rs200865199
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_003098.3(SNTA1):c.1157C>T(p.Pro386Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P386P) has been classified as Likely benign.
Frequency
Consequence
NM_003098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNTA1 | NM_003098.3 | c.1157C>T | p.Pro386Leu | missense_variant | 6/8 | ENST00000217381.3 | |
LOC124904889 | XR_007067567.1 | n.257G>A | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNTA1 | ENST00000217381.3 | c.1157C>T | p.Pro386Leu | missense_variant | 6/8 | 1 | NM_003098.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000638 AC: 16AN: 250644Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135614
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461662Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727142
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15AN XY: 74496
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 391855; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function - |
Long QT syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 18, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 386 of the SNTA1 protein (p.Pro386Leu). This variant is present in population databases (rs200865199, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 391855). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SNTA1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at